When two solutions having different concentrations of a dissolved substance, or solute, are separated from each other by a semi-permeable membrane, permeable only to a solvent, it is found that solvent passes from the less concentrated solution to the more concentrated solution more rapidly than from the more concentrated to the less concentrated solution. This tends to equalize the concentrations of the dissolved substance in the two solutions. This process is called osmosis.
Laboratory measurement of osmosis is often done with a U-tube or similar device as shown in FIG. 1. The U-tube is divided at its base by a semi-permeable membrane. Supposing now that Side A contains a solution in which the solute sugar is dissolved in the solvent water. Side B contains an equal quantity of pure water and both sides are subject to the same initial temperature and pressure. If the membrane is permeable to water and not to sugar, water molecules will be able to pass in both directions from A to B and B to A.
Water molecules will traverse the membrane from B to A much more often than from A to B because water will tend to move from a solution with fewer dissolved particles per unit volume to a solution with more dissolved particles per unit volume. This is because the chemical potential (free energy per mole) of a solvent is decreased if other substances are dissolved in it. The decrease of free energy of the solvent varies directly with the number of dissolved particles per unit volume.
FIG. 2 shows that as a net result, column A becomes higher than column B. An equilibrium is reached when the increased pressure of column A exerted on the solution is great enough for water molecules to be forced to cross the membrane from A to B as fast as they move into A from B. When this point is reached, water is passing through the membrane in opposite directions at the same rate and the system is in equilibrium. In this case, the osmotic equilibrium pressure upon the solution is produced by gravity, but this is not necessarily the case.
In a closed system where two volumes are held in closed containers, the increase in volume of liquid on one side of the membrane nd the decrease in the other will result in a net pressure differential equivalent to the hydrostatic gravitational pressure of the above example. Osmotic pressure is therefore defined as the algebraic sum of that positive and negative pressure which must be exerted on the solution and the solvent respectively in order to keep solvent transfer from the solution in equilibrium with solvent transfer from pure solvent when the two volumes are separated by a semi-permeable membrane.
Any solution or colloid fluid can be described as having a characteristic potential osmotic pressure. Osmotic pressure of a solution of colloid is therefore a measure of the tendency of solvent to move into it by osmosis. Osmotic pressure of colloids is also known as oncotic pressure.
Osmometers presently known in the art are subject to a number of limitations which detract materially from their medical usefulness and the efficiency of measuring oncotic pressures. For example, osmotic studies of biological fluids by conventional methods require relatively large liquid volumes or disposable samples and excessive amounts of time.
There is also the need for maintaining precise temperature control and proper semi-permeable membrane characteristics during the time it takes to record osmotic pressure. Conventional osmometers have not been able to take a measurement in a short enough time so as to be consistently usable either in an in vivo environment or when osmotic pressures are very high.
I have previously disclosed in my U.S. Pat. No. 3,063,288 a method and apparatus for measuring colloid osmotic pressures. While this apparatus has been useful in measuring the osmotic pressure of small amounts of solutions, it is not amenable to the purpose of this invention. I have revised and improved upon the principles of that invention to allow for osmotic readings to be made in vivo and in highly concentrated solutions in a much shorter amount of time.
Because of their shortcomings, conventional osmometers have not been useful in many medical areas in which water balance is a primary concern. Water balance is particularly of concern in the study of aging. It has been determined that the percentage of water in the human body decreases as a person ages. For example, an embryo is 90% water, a fetus and newborn child is 80%, a mature adult 70%, and an older adult may have percentages of body water in the 60's or even 50's. It is suspected that there is some profound relationship between water and aging. A way of measuring the loss of water in cells in the body is by measuring osmotic pressure. The physical phenomenon controlling water in cells is the oncotic pressure (colloid osmotic pressure) due to the presence of macromolecules, large protein molecules, within the cell. It is through study of this osmotic relationship in the cell that one might be able to understand some of the changes that occur with aging.
An improved osmometer would also be useful in the study of sickle-cell anemia. Sickle-cell anemia is a disease in which the hemoglobin in red blood cells, when exposed to low partial pressures of oxygen, contracts into an aggregate called a tactoid. The tactoid appears to occur when the cell water diffuses out of the cell due to solute-solute interaction of aggregating hemoglobin, a macromolecule. The aggregation of the hemoglobin molecules disrupts the osmotic equilibrium within the cell to the point where the solvent (water) cannot be retained within the sickle cell. The dehydrated cell then becomes sickled and is unable to operate effectively in transporting oxygen in the body. If a way could be found to reduce the solute-solute interaction, and the subsequent water loss, the sickling phenomena might be interrupted.
Control of intravascular blood volume through osmotic pressure is an important element in kidney dialysis and intravenous saline infusion. The rate of infusion of fluid into a patient in either of these situations must be carefully controlled. If the saline or dialysis increases the volume of fluid solvent in the patient beyond the normal limits, patients may suffer from hypervolemia which can produce congestive heart failure or pulmonary edema. Conversely, too little fluid solvent in the system may result in hypovolemia which produces hypotension and shock. It is therefore reasonable to expect that constant on-line measurement of intravascular colloid osmotic pressure would be useful for controlling either kidney dialysis or intravenous saline infusions as currently practiced in the medical world.
Another use for osmotic measurement for regulated control of body fluids is in space flight. Currently the only people going to and from the space environment are American and Soviet astronauts in top physical form. In the near future less physically trained personnel will be undergoing the transition to and from the space environment. When a person travels into space, the gravitational field changes and approaches zero; therefore, the gravitational pressure or hydrostatic pressure head of the cardiovascular system also goes to zero. This hydrostatic pressure head is important in maintaining osmotic equilibrium in the body. Transport of water into the vascular system rises with this physiological change and can result in an overload of the circulatory system as in the previously described hypervolemia. On initial exposure to the space environment, an astronaut's vascular system may be excessively stressed from the rise in intravascular volume due to transport of solvent into the vascular system. This might result in a fatal cardiovascular load for some personnel. The converse results in a return from zero gravity to earth. On returning to earth, astronauts have fainted in part due to decreases in plasma volume. This has been particularly true in long duration space flight. Currently the United States, European nations and the Soviet Union have plans to launch manned space stations. The personnel sent to these space stations will live there for long durations which will make them more susceptible to hypovolemia on their return. It is therefore important to mitigate these osmotic stresses on voyages to and from space.
A mitigation of space related colloid osmotic problems would allow for the transport of sick and injured patients into the space environment. Through in vivo colloid osmotic controls, a space hospital might be able to safely receive patients burned over large parts of their bodies, or paralyzed patients. Such patients, freed from gravitational stresses, might be able to function more adequately and be treated more effectively. Burn and paralyzed patients would not have to be turned to avoid pressure sores, and paralyzed patients, freed from the force of gravity might, with the minimal amount of strength they have remaining, be able to function more effectively. Through control of intravascular colloid osmotic pressure, patients would be able to get into space without being subject to mortal stresses upon route. Furthermore, the same sort of colloid osmotic control may be necessary on return to earth from long duration space missions.